Contact phase inhibitors: the future of anticoagulation?

Abstract Thrombosis remains a major public health problem. Although traditional anticoagulants, vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) have been used with success over the last decades for prevention of venous thromboembolism (VTE) and stroke in non-valvular atrial fibrillation (AF), their use exposes the patient to an increased risk of bleeding. To overcome these limitations, new approaches are exploring contact phase inhibitors, specifically targeting factors XI, XIa, XII, and XIIa. Contact phase inhibitors including antisense oligonucleotides, monoclonal antibodies, small peptidomimetic molecules, aptamers and natural inhibitors seem promising in term of efficacy and safety. A common assay can be used to measure the anticoagulant activity of different drugs within a same pharmacological class (INR for VKAs) or even across different pharmacological classes (anti-Xa for all heparins and for direct factor Xa inhibitors). Because of the diversity of contact phase inhibitors, no specific common assay has been proposed so far. Activated partial thromboplastin time (aPTT) could play a role in the assessment of these new anticoagulants, but its relevance need to be confirmed. We aim at providing an overview of the pharmacological properties of contact phase inhibitors, the safety and efficacy outcomes from clinicals trials, as well as the possible coagulation assays relevant for patient follow-up.